High levels of potassium in the blood (called hyperkalemia) is unpredictable and can be life-threatening. It can cause serious heart problems and sudden death.1-3 There are often no warning signs, meaning a person can have high potassium without knowing it.4
If symptoms do occur, they are often nonspecific such as heart palpitations, nausea, weakness, or paresthesia.5 Paresthesia is an abnormal sensation of tingling, numbness, or burning that is usually felt in the hands, feet, arms, or legs.
Blood potassium >5.0 indicates potassium imbalance.6 Arbitrary thresholds are used to indicate degree of severity, such as mild (>5.0), moderate (>5.5), and severe (>6.0).5,7 Clinical severity is determined by the speed of onset, magnitude of the severity, and the development of clinical findings.4
Hyperkalemia is further classified as chronic or acute.5 Acute hyperkalemia represents a single event, occurring over hours to days and usually requires emergency treatment. Chronic hyperkalemia develops over the course of weeks to months, may be persistent or develop periodically, and requires ongoing outpatient management.
A person's potassium levels can be easily checked with a simple blood test. The healthcare provider draws a small blood sample, and sends it to a laboratory for analysis. This is usually part of a routine blood test given during a physical exam. It is often performed as part of a basic metabolic panel, which checks for several conditions, including kidney function and diabetes.
Prevalence of Hyperkalemia
The true incidence and prevalence of hyperkalemia is not known, but it has been estimated to be 2-3% in the general population;7,8 and 1% to 10% among hospitalized patients.1,9,10
People with chronic kidney disease, heart failure, diabetes mellitus, and those taking blood pressure medicines called renin-angiotensin-aldosterone system inhibitors (RAASi) have an estimated 2 to 3 times higher risk for hyperkalemia.3,9,11
More than half of predialysis CKD patients develop hyperkalemia.12,13
Diagnosis and Management of Hyperkalemia
Diagnosis includes assessment of kidney and heart function, including blood tests and electrocardiogram (ECG) to determine whether the hyperkalemia requires immediate emergency treatment.5,6,14 An ECG is a test that checks for problems with the electrical activity of the heart.
The choice of treatment is determined by the patient's clinical presentation, how rapidly the disorder developed, severity of hyperkalemia, and by the presence or absence of ECG changes.6
The faster the rise in serum potassium and the greater the evidence of toxicity, the more aggressive the treatment will need to be.5
Treatment for acute hyperkalemia involves stabilzing heart function, shifting potassium to the intracellular space [using a combination of IV insulin plus glucose (to offset hypoglycemia), albuterol and sodium bicarbonate], and removing potassium with potassium binders, diuretics, or dialysis.6,15
Management of chronic hyperkalemia requires confirmation, increased laboratory surveillance, dietary review and counseling, a review of medications (prescribed, over-the-counter and herbal), and, if needed, a potassium-lowering medication and/or a diuretic.15,16
New potassium-lowering medications have recently been developed:
Patiromer, which was approved by the FDA in October 2015, binds potassium in the gastrointestinal tract (primarily in the colon).16 It should not be used as an emergency treatment for life-threatening hyperkalemia because of its delayed onset of action. It is a dry powder that is mixed with water and taken by mouth.17,18
Sodium zirconium cyclosilicate (ZS-9), which is currently under review by the FDA,19 binds potassium in the gastrointestinal tract. It has been studied in three double-blind, placebo controlled trials and in one ongoing 12-month open label clinical trial in patients with hyperkalaemia, which represents over 1,600 patients treated. It comes in a powder that is mixed with water and taken by mouth.16
Published studies to date demonstrate that both patiromer and ZS-9 can safely and effectively reduce potassium levels in patients with diverse underlying diseases, including heart failure and chronic kidney disease.20-23
Dietary factors (high-potassium foods, additives, and/or salt substitutes) and comorbid conditions (e.g., CKD, heart failure) can contribute to hyperkalemia. However, drug-induced hyperkalemia is considered the most important cause of high potassium in everyday clinical practice.24
Prescription and nonprescription drugs have been identified as a primary or contributing cause in 35-75% of hospitalized patients with hyperkalemia.24,25
In a study of 168 patients with severe hyperkalemia detected at or during hospital stay, 60% were taking at least one drug known to cause or worsen hyperkalemia. In 10% of these cases, death could be attributed to hyperkalemia.26
A wide range of drugs can induce hyperkalemia, but the main culprits are those that target the renin-angiotensin-aldosterone system (RAAS), including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Potassium-sparing diuretics, beta-blockers, NSAIDs, calcineurin inhibitors, potassium-based salt substitutes, potassium dietary supplements, heparin, trimethoprim (an antibiotic), and several others can also contribute to hyperkalemia.15
Treatment with RAAS inhibitors is a widely-used therapy to reduce progression of CKD. RAAS inhibitors have also been shown to reduce illness and death in patients with heart failure. Yet they are often discontinued or under-prescribed in order to manage potassium levels, which may diminish or eliminate their potential morbidity and mortality benefit.12
The emergence of two new potassium binders, sodium zirconium cyclosilicate (ZS-9) and patiromer, may enable the more liberal use of RAAS therapy, even in patients who are prone to hyperkalemia. There is speculation that this may result in improved outcomes in patients with cardiovascular and kidney diseases.7,12,23
Kidney Disease and Hyperkalemia
Under normal circumstances, the kidneys are responsible for excreting 90% of the potassium that is consumed daily, with the remaining 10% excreted by feces.4,9,27,28
People with chronic kidney disease (CKD) have a high risk for hyperkalemia, due in part to the effects of kidney dysfunction on potassium homeostasis.20,29
A recent review reports hyperkalemia frequency as high as 40-50% in people with chronic kidney disease compared to 2-3% in the general population.7,8,16 CKD patients with the highest risk include those with diabetes, cardiovascular disease, advanced CKD, transplant recipients, and patients taking renin-angiotensin aldosterone system (RAAS) inhibitors.16
An episode of hyperkalemia in patients with CKD increases the odds of mortality within one day of the event.30
Hyperkalemia is also common in kidney transplant recipients who receive immunosuppressive therapy with calcineurin inhibitors (cyclosporine or tacrolimus), with a reported incidence of 44% to 73%. The use of ACE inhibitors and angiotensin-receptor blockers to slow the progression of chronic allograft nephropathy increases the risk.31
Heart Failure and Hyperkalemia
Approximately 26 million people worldwide have heart failure (HF). Because of their disease, comorbidities, and medical therapy, these patients have an increased risk for hyperkalemia.9
Disorders of potassium homeostasis can increase the already elevated risk of arrhythmia in patients with heart failure. HF patients have a high prevalence of chronic kidney disease, which further heightens the risk, especially in those treated with renin-angiotensin-aldosterone system inhibitors.9 In 105,388 heart failure patients enrolled in the ADHERE study, more than 60% had kidney disease.9,32
In HF patients with CKD, the prevalence of hyperkalemia can be up to 20% and is associated with an increased risk of mortality and major adverse cardiovascular events..9,33
The overall prevalence of CKD in the U.S. population is approximately 14.8 percent.34
High blood pressure and diabetes are the main causes of CKD. Almost half of individuals with CKD also have diabetes and/or self-reported cardiovascular disease (CVD).35
Kidney disease often has no symptoms and, in its early stages, can go undetected. For this reason, kidney disease is often referred to as a "silent disease."35
According to the 2016 USRDS report, CKD is more common than diabetes mellitus in the United States; an estimated 14.8% of adults have CKD, compared to 12.3% with diabetes mellitus.34
Thirty-three percent of U.S. adults over the age of 40 live with chronic kidney disease (CKD).36
More than 37 million people in the U.S. have CKD,37 and over 80% don't know they have it.38,39 According to a large representative telephone-based survey by the centers for disease control (CDC), the prevalence of self-reported CKD ranges from 1.8% in Virginia to 4.0% in Arizona. Given the overall prevalence of CKD in the U.S. of 14.8%, these numbers are consistent with limited awareness of CKD among those who have the condition.34,40
There has been little improvement over the last 16 years in the numbers of people with CKD who are aware of their disease.34
African-Americans are about 3.5 times more likely to develop kidney failure than Caucasians.35
Hispanics are about 1.5 times more likely to develop kidney failure than non-Hispanics.35
A total of 1,462 children in the United States began treatment for kidney failure in 2013, and 9,921 children were in treatment for kidney failure on December 31, 2013. The most common initial treatment modality among children overall was hemodialysis (56%).35
The number of children listed for incident and repeat kidney transplant was 1,277 in 2013.35
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Anker SD, Kosiborod M, Zannad F, et al. Maintenance of serum potassium with sodium zirconium cyclosilicate (ZS-9) in heart failure patients: results from a phase 3 randomized, double-blind, placebo-controlled trial. Eur J Heart Fail. Oct 2015;17(10):1050-1056.
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